Increased parenchymal damage and steatohepatitis in Caucasian non-alcoholic fatty liver disease patients with common IL1B and IL6 polymorphisms
| Autor: | Nelson, JE, Handa, P, Aouizerat, B, Wilson, L, Vemulakonda, LA, Yeh, MM, Kowdley, KV, NASH Clinical Research Network |
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| Rok vydání: | 2016 |
| Předmět: |
Liver Cirrhosis
Adult Male Genotype Biopsy European Continental Ancestry Group Interleukin-1beta Chronic Liver Disease and Cirrhosis Clinical Sciences White People Oral and gastrointestinal Hepatitis Non-alcoholic Fatty Liver Disease Genetics NASH Clinical Research Network Humans 2.1 Biological and endogenous factors Aetiology Polymorphism Alleles Nutrition Gastroenterology & Hepatology Whites Interleukin-6 Liver Disease Single Nucleotide Pharmacology and Pharmaceutical Sciences Middle Aged Logistic Models Liver Female Digestive Diseases |
| Zdroj: | Alimentary pharmacology & therapeutics, vol 44, iss 11-12 |
| ISSN: | 1049-9563 |
| Popis: | BackgroundNon-alcoholic fatty liver disease (NAFLD) is a complex, multifactorial disease affected by diet, lifestyle and genetics. Proinflammatory cytokines like IL-1β and IL-6 have been shown to be elevated in non-alcoholic steatohepatitis (NASH).AimTo investigate the relationship between IL1B and IL6 gene polymorphisms and histological features of NAFLD in the NASH CRN cohort.MethodsA total of 604 adult (≥18 years) non-Hispanic Caucasians with biopsy-proven NAFLD were genotyped for the following SNPs: IL1B, rs16944, rs1143634; IL6, rs1800795, rs10499563. Logistic regression was used to examine the relationship between genotype and a definitive diagnosis and advanced histological features of NASH after controlling for the following variables selected a priori: age, sex, diabetes, obesity and HOMA-IR level.ResultsThe IL6 rs10499563 C allele was independently associated with the presence of definitive NASH, and increased ballooning and Mallory bodies. The IL1B rs1143634 TT genotype was associated with advanced fibrosis and increased Mallory bodies. The IL6 rs1800795 C allele was associated with not only increased risk for severe steatosis, >66% but also decreased risk for advanced fibrosis and lobular inflammation and Mallory body formation.ConclusionsThese results suggest that common variants in the IL6 and IL1B genes may increase susceptibility for NASH and confer a higher risk of hepatic parenchymal damage including increased ballooning, increased Mallory bodies, and bridging fibrosis or cirrhosis. In contrast, the IL6 rs1800795 C allele may confer a higher risk for steatosis, but less parenchymal damage. Our findings support the development of therapeutics aimed at IL-1β and IL-6 suppression. |
| Databáze: | OpenAIRE |
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